The primary circadian clock in mammals is located in the The ECS could interact with the serotonergic system in. Cannabis, Sleep and Nutrition: How the Endocannabinoid System Affects Our Circadian Rhythm. Presented by PlusCBD Oil. April 26, This article is. Your circadian rhythm is a daily (~24 h) cycle of biological activity. CBD directly interacts with receptors of the endocannabinoid system and has been found to.
System, and CBD, the Rhythms Endocannabinoid Circadian
Possible mechanisms by which endocannabinoid signalling ECS could contribute to the feeding and metabolic changes that occur during the late-summer hyperphagic period and during the period of hibernation. The duration of day-time sunlight photoperiod synchronizes the circannual rhythms of hibernation, but torpor induction requires both a short photoperiod and low environmental temperature Heldmaier et al. This combined need could relate to the animal's thermogenic capacity, as short photoperiod and cold together maximally increase brown adipose tissue mass, expression of mitochondrial uncoupling protein and lipolytic enzymes and sympathetic innervation Cannon and Nedergaard, The body mass cycle is regulated by a circannual clock Lee and Zucker, ; Zucker, Return to natural conditions resets the period to nearly a year, suggesting that, like the circadian clock, the circannual clock is entrained by environmental light and temperature.
The circannual hibernation cycle is characterized by shifts from normal feeding to hyperphagia to hypophagia. A key mediator of the circannual cycle of feeding behaviour is the anorexigenic hormone, leptin Scarpace and Zhang, In black bears, circulating leptin increases in late summer, remains high during hibernation and decreases in spring Donahue et al. Increased concentrations of leptin during hibernation are consistent with the profound hypophagia that occurs during hibernation, and decreased concentrations of leptin in spring likely allow for spring feeding.
Leptin infusion in arctic ground squirrels following emergence from hibernation prevents hyperphagia Boyer et al. The occurrence of hyperphagia in late summer despite high leptin concentrations in black bears Donahue et al.
Consistent with this hypothesis, brown bats become leptin resistant during the period of maximal fat deposition Kronfeld-Schor et al. ECS regulates orexigenic drive in reward-related brain regions and in the primary orexigenic nuclei of the hypothalamus.
Recent evidence demonstrates that food consumption is characterized by learned habits and can be motivated by reinforcers Volkow and Wise, There is clear evidence that ECS modulates the rewarding properties of food Kirkham et al. CB 1 receptors are present in several primary relay nuclei of the reward pathway, including the prefrontal cortex Eggan and Lewis, and the nucleus accumbens Lupica and Riegel, Injection of 2-AG into the shell of the nucleus accumbens results in increased food intake Kirkham et al.
The drive to eat is also regulated by the hypothalamus, and ECS occurs at multiple sites within the hypothalamic circuits involved in metabolic regulation Cota et al. Furthermore, injection of AEA into the ventromedial hypothalamus of satiated rats results in CB 1 receptor-mediated hyperphagia Jamshidi and Taylor, , suggesting that increased ECS over-rides normal satiety signals to induce inappropriate food consumption. In the context of the cycle of hibernation, this mechanism could be beneficial during the late-summer hyperphagic period Figure 4.
A milestone in our understanding of the role of ECS in the regulation of satiety came from studies of Di Marzo and Kunos demonstrating that ECS is an important effector of leptin in the hypothalamus. In particular, leptin reduces hypothalamic contents of AEA and 2-AG in normal mice, and mice deficient in leptin signalling are obese and hyperphagic, and have elevated hypothalamic endocannabinoid contents Di Marzo et al. Blockade of the CB 1 receptor in these mice results in decreased food intake, indicating that at least part of the anorexigenic effect of leptin is due to decreased ECS.
Recent evidence also suggests that increased CB 1 receptor activity is involved in the orexigenic effects of NPY Gamber et al. There is evidence that loss of leptin-induced inhibition of ECS could contribute to some forms of leptin resistance Osei-Hyiaman et al. Overall, the tight relationship between leptin and ECS in the hypothalamus, together with the data discussed above that leptin is a critical mediator of the transitions between late summer and hibernation, and between hibernation and spring feeding, suggests the hypothesis that ECS is involved in the regulation of feeding in animals with a circannual cycle.
Increased body mass in hibernators is largely due to increased lipid storage in white adipose tissues WATs , and it is hypothesized that this process has a set point that varies circannually Davis, ; Mrosovsky and Faust, ; Dark, Consistent with this hypothesis, limiting the foraging time of ground squirrels leads to decreased lean body mass, but WAT fat stores are conserved Bachman, Hibernators also exhibit dramatic shifts in cellular sources of metabolic fuel. During active periods, both carbohydrates and lipids are used Buck and Barnes, ; Squire et al.
Conversely, during torpor, metabolic needs are met exclusively by oxidation of fatty acids FAs. Key molecular switches in cellular metabolism include the kinase Akt Miyamoto et al.
Activation of Akt by insulin receptor signalling increases utilization of carbohydrates as cellular energy sources.
Consistent with a shift to lipolysis during hibernation, torpor is associated with significant decreases in Akt activity Cai et al. Recent data in human skeletal muscle suggest that CB 1 receptor activation, perhaps in response to AEA released from adipocytes, negatively regulates insulin stimulation of Akt activation Eckardt et al.
These data lead to the notion that adipose-derived endocannabinoids could modulate the switch between carbohydrate and lipid utilization during torpor Figure 4. Another key determinant of the cellular energy source is pyruvate dehydrogenase kinase 4 PDK4 Roche and Hiromasa, PDK4 inactivates pyruvate dehydrogenase, which leads to decreased glycolysis and increased FA oxidation.
PDK4 expression is increased during hibernation Andrews et al. Interestingly, PDK4 expression appears to be tonically maintained by CB 1 receptor activation in skeletal muscle cells from both lean and obese humans Cavuoto et al. There is clear evidence that ECS signalling occurs in adipose tissue and functions to regulate energy homeostasis. In particular, CB 1 receptor blockade results in enhanced lipolysis in WAT through stimulation of enzymes involved in beta-oxidation and the tricarboxylic acid cycle; increases energy expenditure in adipose tissue via futile cycle induction; and up-regulates expression of glucose transporter type 4, resulting in improved glucose utilization Jbilo et al.
Adipocytes also function as endocrine cells, releasing the adipokines adiponectin and visfatin. Adiponectin is an insulin-sensitizing hormone with anti-inflammatory properties Kadowaki and Yamauchi, Visfatin is a recently discovered adipokine capable of activating the insulin receptor and thought to promote obesity Marra and Bertolani, CB 1 receptor activation in WAT inhibits the secretion of adiponectin and increases the secretion of visfatin, an effect that will favour insulin resistance and weight gain Perwitz et al.
Taken together, these data suggest that high ECS in WAT is associated with lipid storage, and more significantly, could be required for lipid storage to occur. In the context of hibernation, these findings suggest the hypothesis that adipocyte ECS would be high during the late summer and very low during the hibernation phase Figure 4. ECS in the liver is also emerging as an important player in metabolic regulation. Activation of the CB 1 receptor in hepatocytes results in increased expression of several genes involved in de novo synthesis of FAs, including the lipogenic transcription factor, SREBP-1c Osei-Hyiaman et al.
Recent studies utilizing mice with cell-specific deletions of the CB 1 receptor in hepatocytes strongly suggest that many of the effects of ECS on metabolism are mediated by the liver Osei-Hyiaman et al.
In particular, these mice became obese when fed a high-fat diet, but did not develop hepatic steatosis, insulin resistance or leptin resistance to the degree of wild-type controls. As in the WAT, high ECS tone in the liver is consistent with the pre-hibernation phase in which metabolic fuel is preserved and stored for later use Figure 4. WAT and cellular phospholipids from hibernating animals are relatively rich in polyunsaturated FAs PUFAs , and the increased lipid fluidity that results is thought to benefit the animal at lower T b.
Evidence suggests that the FA composition of lipids in hibernating animals has a profound effect on torpor bouts, with significantly longer bouts in animals on PUFA-rich diets Florant et al. Central to the latter process is the enzyme monoacylglycerol acetyltransferase MGAT. MGAT is highly expressed during hibernation Mostafa et al.
Ground squirrels also exhibit significantly lower activity of cytosolic phospholipase A 2 activity during hibernation Woods and Storey, , a change that would both reduce the generation of oxidation products of arachidonic acid and preserve phospholipid arachidonate. The endocannabinoids are arachidonate derivatives that target the CB receptors.
In addition, several studies suggest that they could function as arachidonate donors, in particular under conditions in which arachidonic acid is shuttled from cell to cell Pratt et al. Therefore, the concept that PUFAs such as arachidonic acid are handled differently during hibernation could have interesting implications for ECS.
Among many other possibilities, perhaps a reduction in the availability of arachidonic acid for signalling purposes results in reduced ECS, which in turn contributes to the switch from fat storage to fat mobilization during hibernation. Despite the intriguing overlaps between ECS function and hibernation, to our knowledge, there are no published reports on the role or regulation of the ECS in hibernators. As a first step in addressing this question, plasma lipids from summer-active SA and torpid T Marmota monax common names are groundhog and woodchuck were analysed using LC—MS for the two endocannabinoids and several related lipids Figure 5.
Interestingly, concentrations of 2-AG could not be detected in plasma from any of the M. In contrast, AEA was detectable in M. The concentration of AEA was not different in plasma from M. In contrast, plasma concentrations of palmitoylethanolamide PEA and 2-oleoylglycerol 2-OG increased during torpor, whereas concentrations of oleoylethanolamide OEA decreased. PEA has prominent anti-inflammatory properties and could contribute to suppression of immune function during hibernation.
OEA has been hypothesized to enter the circulation from metabolism of dietary fat and to function as a satiety factor Fu et al. Its reduced concentration in the plasma of hibernating thus, not feeding M. The function of 2-OG has not yet been elucidated. Endocannabinoid and family members were determined in plasma from Marmota monax during the summer active period active and during a torpor bout in the hibernation period hibernating. Plasma samples were purchased from Northeastern Wildlife Harrison, ID, USA ; the samples were from both male and female animals, and similar proportions of each sex were represented in each time period.
Each bar is the mean of three to five plasma samples; vertical bars represent SEM. Thus, the pattern of plasma NAEs could be both the result of, as well as the modulator of, unique hibernation-associated biological processes.
The roles of the endocannabinoids and their structural cousins in hibernation remain a rich area for future research. Many physiological functions are regulated by circadian rhythms, and data are accumulating that dysregulation of circadian rhythms or a mismatch between circadian rhythmicity as occurs in modern human society contribute to human diseases Takahashi et al. Bipolar disorder and depression are serious human psychiatric disorders for which circadian dysregulation is a contributing or causative factor.
For example, Clock mutant mice exhibit a behavioural phenotype that includes many components of mania: Cannabis use increases the number or duration of manic episodes, and chronic exposure of humans to Cannabis correlates with an increased incidence of bipolar disorder Strakowski and DelBello, Cannabis consumption in humans is associated with increased likelihood of developing bipolar disorder; perhaps interactions of THC with circadian rhythms contribute to this mechanism.
Although the study of hibernation seems distant from human biology, there are several likely sites of interaction. For example, enhanced understanding of the processes that protect organs during hibernation could increase organ preservation strategies for transplantation, or during organ failure in diseased humans.
On the other hand, understanding the molecular mechanisms involved in hyperphagia and nutrient storage that occur in the period preceding hibernation could shed light on the mechanisms of human obesity. National Center for Biotechnology Information , U. Journal List Br J Pharmacol v. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC.
Abstract Endogenous cannabinoid signalling is widespread throughout the body, and considerable evidence supports its modulatory role in many fundamental physiological processes. N -arachidonylethanolamine, anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide, 2-oleoylglycerol, cannabinoid, CB1 receptor, diurnal, circadian, hibernation, circannual, sleep deprivation. Introduction We live in a world in which periodic environmental change, driven by geophysical cycles, dominates the activity of life Foster and Roenneberg, The circadian rhythm of ECS components There is evidence that ECS exhibits a circadian rhythm with variations reported in endocannabinoid tissue contents Valenti et al.
Open in a separate window. Time of day and sleep deprivation affect plasma endocannabinoids in humans The endocannabinoids are also present in the circulation, although their source and targets are not well understood. ECS and circadian rhythms The primary circadian clock in mammals is located in the SCN, a distinct group of cells located in the hypothalamus. CBs and the circadian rhythm of temperature There is considerable evidence that exogenously administered CB 1 receptor agonists affect body temperature regulation.
Hibernation is an extreme example of seasonal rhythm Hibernation includes regulated decreases in body temperature T b , heart rate, respiration and metabolic rate Zucker, ; Carey et al. Circannual cycle and feeding behaviour The circannual hibernation cycle is characterized by shifts from normal feeding to hyperphagia to hypophagia.
ECS and feeding behaviour ECS regulates orexigenic drive in reward-related brain regions and in the primary orexigenic nuclei of the hypothalamus. Circannual cycles of lipid and carbohydrate metabolism Increased body mass in hibernators is largely due to increased lipid storage in white adipose tissues WATs , and it is hypothesized that this process has a set point that varies circannually Davis, ; Mrosovsky and Faust, ; Dark, ECS and lipid storage There is clear evidence that ECS signalling occurs in adipose tissue and functions to regulate energy homeostasis.
Changes in cellular lipid composition during hibernation WAT and cellular phospholipids from hibernating animals are relatively rich in polyunsaturated FAs PUFAs , and the increased lipid fluidity that results is thought to benefit the animal at lower T b.
Changes in circulating concentrations of N -acylethanolamines during hibernation Despite the intriguing overlaps between ECS function and hibernation, to our knowledge, there are no published reports on the role or regulation of the ECS in hibernators.
Summary and concluding remarks Many physiological functions are regulated by circadian rhythms, and data are accumulating that dysregulation of circadian rhythms or a mismatch between circadian rhythmicity as occurs in modern human society contribute to human diseases Takahashi et al.
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Orexins and orexin receptors: Results Probl Cell Differ. Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nuclei. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. These balancing effects may positively impact your sleep habits and quality. Many athletes and active folks who regularly take CBD oil have reported back that they feel the supplement has a soothing, calming effect.
Studies on CBD oil for sleeping suggest that lower servings of CBD may actually have awakening properties, while higher doses promote more sleep. One study found that CBD reduced periods of wakefulness or restlessness and increased total sleep time.
Is CBD right for you? Find out more here. People often wonder whether CBD helps you sleep better than smoking marijuana. The truth is, the two have very different effects on sleep. Marijuana is different from hemp-derived CBD oil in that it contains significantly higher levels of THC, the major cannabinoid that causes a high.
These euphoric effects of THC, particularly from indica marijuana strains, have been known to induce heavy and intense sedating effects.
While smoking marijuana can make you intensely sleepy and flat out numb your body, it also may inhibit REM rapid eye movement sleep , which is the restorative part of the sleep cycle and when dreams occur.
This may leave you feeling foggy and lethargic when you wake up the next morning. While some have described it as causing relaxing effects, this is far different from the psychoactive and sedative effects that are created with smoking marijuana.
Used as a supplement, CBD oil naturally can encourage a healthy sleep cycle through its support of the endocannabinoid system. Individuals have different needs, and you may find that you react to CBD differently than someone else. The best CBD dosage and timing to take CBD supplements depends on your needs and how your endocannabinoid system responds.
Figuring out when and how much CBD you should take to promote better sleep just takes a short trial period. Many athletes prefer to take their CBD supplements first thing in the morning, perhaps mixed into their coffee or breakfast. Others find that taking their CBD after a strenuous workout, or even with dinner or before bed works best. If CBD oil supplements make you feel relaxed, taking them in the evenings is likely more ideal.
To figure out how much CBD you should take , it is suggested that you start with a lower potency and gradually work your way up as needed.
Gradually increase your serving every day, or week, while monitoring how it influences your sleep quality. This will help you dial in on the optimal CBD serving that works best for you to encourage better sleep habits.
The 49+ Benefits of THC, CBD, and The Endocannabinoid System
The 49+ Benefits of THC, CBD, and The Endocannabinoid System. August 29, Helps with sleep. May Interact with circadian rhythm. The endocannabinoid system features receptor sites that are referred to to regulate our circadian rhythm and control our sleep-wake cycles. CBD co-administered with THC improves sleep more efficaciously than regulated by circadian rhythms and the endocannabinoid system.